Richard J. Pariza

Metalloporphyrins as chemical mimics of cytochrome P-450 systems

Certain synthetic metalloporphyrins have been shown to mimic the in vivo metabolism of some pharmaceuticals. Oxidation, hydroxylation and N-demethylation yielded synthetic metabolites. If found to be general, this lays the foundation of a predictive basis to optimize analog design of inhibitors with reduced oxidative reactivity, to determine the proclivity of drugs to form biologically active metabolites and provides a convenient methodology for their preparation.

Novel macrolides via meso-tetraarylmetalloporphyrin assisted oxidations

Abstract The oxidation of Clarithromycin A with meso -tetraarylmetalloporphyrins and NaOCl led to the formation of the 3′-NClMe Clarithromycin A ( 5 ) 3′-oxo Clarithromycin ( 6 ) and Clarithromycin A N-oxide ( 4 ).

Synthesis of Novel C2-symmetric and Pseudo C2-symmetric Based Diols, Epoxides and Dideoxy Derivatives of HIV Protease Inhibitors

The Julias olefination reaction between the sulfone derivative (10) and the aldehyde (13) (both obtained from L-phenylalanine) followed by debenzylation led to the formation (2S,5S,3E)-2,5-bis-[(1,1-dimethyl ethoxy)-carbonyl]amino-1,6-diphenylhex-3-ene (4a). Similarly (2S,5S,3E)-2,5-bis-[(1,1-dimethylethoxy)-carbonyl]amino-1-phenyl-6-(p-methoxy)phenylhex-3-ene (4b) was also synthesised from the sulfone (10) and L-tyrosine derived aldehyde (21). These novel intermediates (4a and 4b) were subjected to epoxidation, hydrogenation, hydroboration-oxidation and dihydroxylation reactions. These modifications resulted in the synthesis of known and unknown, C2-symmetric and pseudo-C2-symmetric diamino-epoxides, dideoxy derivatives, diols and deoxy diols based HIV protease inhibitors.

Synthesis of a novel C2-symmetrical (2S,5S)-2,5-bis-[(1,1-dimethylethoxy)carbonylamino]-1,6-diphenylhex-3-ene: Applications in the synthesis of potential HIV protease inhibitors

Abstract The synthesis of a novel and versatile (2S,5S)-2,5-bis-[(1,1′-dimethylethoxy)carbonylamino]-1,6-diphenylhex-3-ene (2) based on Julias olefination strategy coupled with its application in stereoselective preparations of HIV protease inhibitors has been discussed.

Synthesis of the macrolide antibiotic, oxolide

Abstract Oxolide was synthesized from Erythromycin A. Key features include two stereoselective reductions with DIBALH and NaBH3CN and a novel pH dependent purification of the final product. An acid-stable macrolide, oxolide, was synthesized from Erythromycin A. Key features include two stereoselective reductions with DIBALH and NaBH3CN and a simple pH dependent separation of the final product from its C-11 epimer.